Phase insensitive preparation of single-shot rare for diffusion imaging

ABSTRACT

A method for eliminating then on-MG component in RARE imaging that does not require a poor slice profile or discarding a substantial number of echoes (FIG.  2 ). This method relies upon the observation that the magnetization in each component is determined by the phase at one half of the echo time before the first refocusing pulse. A ninety degree pulse applied at this time will rotate one of the components to the longitudinal axis where it will be invisible in the subsequent sequence, (b RF). If the phase of the ninety degree pulse is the same as that of the refocusing pulses, then it will be the non-MG component that is eliminated. The combination of the tailored RF train and this ninety degree pulse permits acquisition of data from the very first echo without artifact (FIGS.  2, 4 ).

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority from U.S. Provisional ApplicationSerial No. 60/081,489, filed Apr. 13, 1998, the contents of which arehereby incorporated by reference.

GOVERNMENT SUPPORT

This invention was supported by funds from the U.S. Government (NationalInstitute of Neurological Disorders and Stroke, grant PO1-NS08803) andthe U.S. Government may therefore have certain rights in the invention.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to diffusion imaging using a magneticresonance imaging device and, more particularly, to a technique formodifying the RARE sequence to eliminate artifacts which relate to thestrong sensitivity of multiple spin echo sequences to the phase of theprepared magnetization so that RARE may be used for diffusion and T₂*imaging.

2. Description of the Prior Art

Recent advancements in scanner hardware and pulse sequence design havemade possible single excitation images of excellent quality based onmultiple spin echo sequences (MSES) such as RARE and GRASE. Thesesequences are an attractive alternative to echoplanar imaging becausethey suffer much less from chemical shift artifact and distortion thanechoplanar. Echoplanar imaging is frequently used for forms offunctional imaging in which a preparation sensitive to physiology isapplied prior to the echoplanar readout. Such an approach can, inprinciple, also be used to prepare MSES.

Those preparation schemes that affect longitudinal magnetization, suchas magnetization transfer saturation, arterial spin tagging, inversionrecovery and saturation recovery, do not affect image quality andconsequently work well with MSES. However, preparation schemes thatalter transverse magnetization such as T₂, diffusion, and T₂*preparation can result in severely degraded images because theyintroduce unknown phase shifts in the transverse magnetization due tomotion, chemical shift or magnetic field inhomogeneity. Most MSES relyon the amplitude stability of the Carr-Purcell-Meiboom-Gill (CPMG)sequence which depends upon the Meiboom-Gill (MG) phase condition so anychanges in the phase of the transverse magnetization caused bypreparation will result in rapid attenuation and modulation of the echoamplitudes causing signal loss and blurring in the images.

For T₂ preparation, phase errors will only occur if the timing of thesequence is inaccurate or subject motion in the presence of therelatively weak crusher gradients causes phase errors. Accurate timingand moderately cooperative subjects will probably be sufficient toobtain good quality T₂ prepared images. T₂ weighting can also beobtained by appropriate phase encode order.

On the other hand, T₂* preparation will only be successful if all spinshave the same chemical shift and the shim is outstanding. Though T₂*weighted images will always exhibit signal loss in voxels where thestatic magnetic field gradient is very large, T₂* prepared MSES imageswill also show severe signal loss or blurring in regions where thestatic magnetic field offset is large. This extra sensitivity to shimmakes conventional T₂* prepared MSES imaging unattractive.

Phase errors due to motion in the presence of large magnetic fieldgradients are the reason for the extreme motion sensitivity ofmulti-shot diffusion imaging. Single-shot echoplanar imaging isfrequently used for diffusion imaging to avoid these motion inducederrors. However, if a phase sensitive MSES is employed for diffusionimaging, severe signal loss and attenuation will occur.

The phase sensitivity of the CPMG sequence is clearly undesirable forthese applications, so ways to avoid this sensitivity must be sought.The simplest approach is to ensure that the refocusing flip angle isexactly 180°. A MSES with exactly 180° refocusing pulses is completelyinsensitive to phase but very small deviations from 180° are sufficientto introduce artifacts. These artifacts are caused by the presence ofmultiple stimulated and spin echo pathways to produce signalcontribution at the echo time. For magnetization satisfying the MG phasecondition, these pathways add constructively and eventually achieve atemporary steady state echo amplitude. If magnetization is 90° from theMG phase, then the pathways interact destructively causing signalamplitude decay and oscillation. In most practical applications,including multi-slice imaging where the flip angle is not uniform acrossthe slice, the flip angle cannot be made close enough to 180° toeliminate signals from these other pathways. In long echo trainapplications, such as single shot imaging, it is also desirable to lowerthe refocusing flip angle to minimize the power deposition in thesubject. The favorable properties of reduced flip angle CPMG sequenceshave been described by Alsop in an article entitled “The Sensitivity ofLow Flip Angle RARE Imaging, ” Magn. Reson. Med., Vol 37, pp. 176-184(1997) and by J. Hennig in an article entitled “Multiecho ImagingSequences with Low Refocusing Flip Angles,” J. Magn. Reson., Vol. 78,pp. 397-407 (1988).

C. S. Poon et al. in an article entitled “Practical T₂ Quantitation forClinical Applications,” JMRI, Vol. 2, pp. 541-553 (1992) proposedcrusher gradient schemes that can eliminate all but the primaryrefocused component. Unfortunately, these schemes require a largecrusher amplitude that increases linearly with echo number. The addedtime required to apply the crusher gradients generally becomesunacceptable after only a handful of echoes. Several investigators havereported such sequences using crusher amplitudes that are too weak tofully dephase an individual voxel. These sequences employednon-selective refocusing pulses very close to 180° so the unwantedsignal components are very weak. The quality of images obtained withslice selective or reduced flip angle refocusing pulses and these weakercrusher gradients would have to be evaluated. This spoiling approach hasbeen employed to acquire. single-shot GRASE diffusion images. Becausevery few spin echoes and many gradient echoes were employed, thesensitivity to chemical shift and susceptibility artifacts wascomparable to echoplanar. The highest quality GRASE images tend toemploy many more radio frequency (RF) pulses and only a few gradientechoes. Spoiling of the CPMG sequence in this way will also cause theecho amplitudes to decrease rapidly with echo number if the refocusingpulse is reduced significantly from 180 degrees so reduction of therefocusing flip angle to lower power deposition is not possible.

A number of modifications to the CPMG sequence have been proposed toreduce errors in T₂ quantification or artifacts in multiple echo imagesby modulating the phase of the refocusing pulses. Some of thesesequences can be interpreted as employing composite 180° pulses whichare more insensitive to RF amplitude errors. Though these sequences workwell for a few echoes when the flip angle is already near 180°, theybegin to fail if the amplitude of the RF is reduced more significantly.They also usually increase the echo spacing and make single shot imagingmore difficult. A two excitation method for producing phase insensitiveimages has also been proposed. Since the source of the phase uncertaintyin diffusion imaging, motion, is not reproducible from excitation toexcitation, the two shot method is not applicable.

An alternate approach to eliminating phase sensitivity of MSES sequencesby crushing only some of the many stimulated and spin echo pathways hasbeen presented by Norris et al. This approach was designed to overcomehardware limitations that precluded the precise timing and controlnecessary to achieve the MG phase condition. Modern clinical hardwarecan now readily achieve the MG condition because RARE has become anessential clinical tool. For the special applications of diffusion andT₂* prepared RARE imaging, however, this approach is still veryimportant. A limitation of the method is the large number of echoeswhich must be discarded before the signal is sufficiently stable tobegin phase encoding.

A refinement of the Norris et al. method is desired that permitsacquisition of data from the very first echo for acquisition ofdiffusion images. The present invention has been developed to meet thisneed in the art.

SUMMARY OF THE INVENTION

The present invention relates to a modification of Multiple Spin EchoSequences (MSES), such as RARE, Fast Spin Echo, and GRASE, which makesimage quality unaffected by the initial phase of the spins. Thismodification makes it possible to acquire images with diffusion or T₂*contrast with a MSES. Diffusion imaging has been shown to be highlyaccurate at the detection of acute stroke and T₂* imaging can be usefulfor detection of hemorrhage and the imaging of certain tissues after theadministration of contrast agents. The images resulting from thismodified MSES sequence are free from the spatial distortion artifactswhich plague the single excitation echoplanar images most widely usedfor diffusion imaging today.

In accordance with the invention, additional dephasing gradients and RFpulses are used to eliminate phase errors that are normally associatedwith diffusion and T₂* single-shot MSES imaging. Following standarddiffusion or T₂* sequences which leave the spins pointing along theplane perpendicular to the scanner magnetic field, a MSES imagingsequence is performed with several modifications which together comprisethe invention. In particular, the invention comprises the steps of:

applying a first dephasing magnetic field gradient to the sample togenerate a magnetization;

applying a first radio frequency pulse to the sample which rotates themagnetization by approximately 90°, the first radio frequency pulsehaving a phase which is the same as a phase of refocusing pulses of aspin echo sequence to be applied to the sample;

applying at least one spin echo sequence whereby a first refocusingpulse of each spin echo sequence occurs at a time after said first radiofrequency pulse which is half a time duration between successiverefocusing pulses of the spin echo sequence, each spin echo sequenceincluding:

a second dephasing magnetic field gradient applied to the sample alongthe same direction as the first dephasing gradient,

a data acquisition period for acquiring data representative of thesample, and

a second radio frequency pulse having a sign opposite the first radiofrequency pulse; and

generating an image of the sample from the data acquired during eachdata acquisition period.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other novel features and advantages of the inventionwill become more apparent and more readily appreciated by those skilledin the art after consideration of the following description inconjunction with the associated drawings, of which:

FIG. 1 illustrates the variation of the Meiboom-Gill (MG) and orthogonalphase components of the echo amplitudes in a multiple spin echo sequence(MSES).

FIG. 2 illustrates sequences for eliminating phase sensitivity in MSES,where FIG. 2(a) illustrates that a dephasing gradient spreads the signalin each voxel evenly between the MG and non MG components and FIG. 2(b)illustrates the addition of a 90° pulse at one half TE before the firstrefocusing pulse to eliminate the non MG component.

FIG. 3 illustrates the phase insensitive pulse sequence employed forimaging using the method of the invention.

FIG. 4 illustrates phantom images demonstrating the effect of the 90°pulse at eliminating the non MG component.

FIG. 5 illustrates axial diffusion images of a normal volunteer acquiredwith single-shot RARE.

FIG. 6 illustrates angular average diffusion images from six axialslices in a patient with stroke symptoms, where the upper row wasacquired with zero diffusion weighting and the lower row is an angularaverage of diffusion images acquired in the three directions.

DETAILED DESCRIPTION OF THE PRESENTLY PREFERRED EMBODIMENTS

A preferred embodiment of the invention will now be described in detailwith reference to FIGS. 1-6. Those skilled in the art will appreciatethat the description given herein with respect to those figures is forexemplary purposes only and is not intended in any way to limit thescope of the invention. All questions regarding the scope of theinvention may be resolved by referring to the appended claims.

Theory

The importance of the phase of the excited magnetization relative to thephase of the refocusing pulses in determining the amplitude of theobserved echoes in a multiple spin echo sequence (MSES) has long beenknown. If the refocusing flip angle is not exactly 180°, the componentof the magnetization along the Meiboom-Gill (MG) phase will beremarkably well refocused while the component orthogonal to this phasewill be modulated and attenuated. This property has recently beenrelated to the existence of a temporary steady state solution to theBloch equations in the absence of T₂ and T1 decay which satisfies theMeiboom Gill condition. The amplitude of the RF pulses can be tailoredto produce a stable MG echo amplitude from the first echo. When such anRF pulse train is applied to magnetization in the orthogonal phase, theecho amplitude rapidly oscillates and decays. Echo amplitudes from thetwo different components for an RF train with refocusing flip angle thatasymptotically approaches 148° are shown in FIG. 1. These amplitudeswere obtained from simulations of the Bloch equations as describedpreviously in the afore-mentioned article by Alsop. T₂ and T1 decay wereneglected. FIG. 1 illustrates the variation of the MG and orthogonalphase components of the echo amplitudes in MSES. As shown, the MGcomponent is highly stable but the orthogonal (non MG) component dropsprecipitously in amplitude and oscillates wildly. An imaging sequenceusing this component will suffer from strong artifacts associated withthis unstable echo amplitude.

When diffusion gradients are applied, motion will introduce a spatiallyvarying phase shift. Typically, motion is sufficiently spatiallycoherent that the phase variation is slow compared to a voxel size. If aRARE sequence is used to image this magnetization, those voxels alongthe MG phase will be perfectly imaged while those with a component alongthe orthogonal phase will be attenuated and will cause image artifactsbecause of the rapid modulation of k-space amplitude and phase. Theresult will be an unacceptable image. In accordance with the invention,this problem is overcome by applying a dephasing gradient prior to theRARE sequence so that each voxel has equal components of MG andorthogonal phase. In addition to the dephasing gradient, rephasinggradients must be added prior to the acquisition of each echo and thenrewound following acquisition to maintain the MG condition. As will bediscussed below, this approach is equivalent to the “displaced U-FLARE”sequence of Norris et al. described in an article entitled “On theApplication of Ultra-Fast RARE Experiments,” Magn. Reson. Med., Vol. 27,pp. 142-164 (1992). The displaced U-FLARE sequence suffered frommodulation of echo amplitudes due to the use of constant flip angle RFpulse trains and the presence of the non MG component signal. Thetailoring of the RF flip angles can readily stabilize the amplitude ofthe MG component. A way to eliminate the non MG component is discussedbelow.

FIG. 2 illustrates sequences for eliminating phase sensitivity in MSES.FIG. 2(a) illustrates that a dephasing gradient spreads the signal ineach voxel evenly between the MG and non MG components, while FIG. 2(b)illustrates the addition of a 90° pulse at one half TE before the firstrefocusing pulse to eliminate the non MG component. This pulse shouldnot be confused with the excitation pulse which usually begins a MSES.

After an initial rapid decline of the signal from the non-MG component,the signal amplitude varies with an approximately sinusoidal patternthat only slowly decays. The period of the sinusoidal modulation varieslinearly with the refocusing flip angle. In Norris et al., a poorrefocusing slice profile is employed to accelerate the decay of the nonMG component. When the flip angle varies across the slice, the differentfrequencies of oscillation lead to a dephasing of the signal. When theslice profile is degraded, the non-MG component is attenuated but noteliminated. Signal on the order of 10% of the image intensity can stillremains after 10 echoes.

The present invention includes a method for eliminating the non-MGcomponent that does not require a poor slice profile or discarding asubstantial number of echoes. This method relies upon the observationthat the magnetization in each component is determined by the phase atone half of the echo time before the first refocusing pulse. As shown inFIG. 2(b), a 90° pulse applied at this time will rotate one of thecomponents to the longitudinal axis where it will be invisible in thesubsequent sequence. If the phase of the 90° pulse is the same as thatof the refocusing pulses, then it will be the non-MG component that iseliminated. The combination of a tailored RF train and this 90° pulsepermits acquisition of data from the very first echo without artifact.

The dephasing of the RARE sequence reduces the signal by a factor oftwo. Consider the spin distribution immediately after the 90 degreepulse. The spins were spread out uniformly in the phase, f, by thedephasing pulse and then the component along the non-MG axis was removedby the 90 degree pulse. The magnetization is therefore given by$\begin{matrix}{M_{x} = {{\cos \quad \phi} = \frac{^{\quad \phi} + ^{{- }\quad \phi}}{2}}} & \lbrack 1\rbrack\end{matrix}$

where M_(x) is the magnetization along the MG phase direction and frepresents the phase added to the magnetization by the dephasinggradient, which is rapidly varying within a single voxel. Prior toacquiring the echoes, a second dephasing pulse is applied with oppositemagnitude causing the magnetization to change, $\begin{matrix}{M_{x}^{echo} = {\frac{1}{2} + \frac{^{{- 2}\quad \quad \phi}}{2}}} & \lbrack 2\rbrack\end{matrix}$

The second term averages to zero within the voxel so only half of theoriginal magnetization is imaged.

The dephasing gradients can be applied in any of the three directions.The choice of the direction depends on the dimensions of the voxel andthe other functions served by the gradients along that direction. Intypical imaging protocols, the slice thickness is greater than thein-plane pixel dimensions and dephasing of the spins is easier along theslice direction. For this reason, the slice direction is typically usedfor the crusher gradients. These crusher gradients cause the signal atthe echo time to consist of a number of components only one of which isvisible. The signal of a spin isochromat can be expanded as$\begin{matrix}{M = {\sum\limits_{n = {{- {echo}}\quad {number}}}^{{echo}\quad {number}}{a_{n}{\exp \left( {\quad n\quad \theta} \right)}}}} & \lbrack 3\rbrack\end{matrix}$

where q is the phase imparted by a pair of crusher gradients pluscontributions from frequency offsets and chemical shift. If thedephasing gradient is also applied along the slice direction, then thephase imparted by the dephasing gradient, f, will have the same spatialdependence and the signal at the echo time will be $\begin{matrix}{M = {{\sum\limits_{n = {{- {echo}}\quad {number}}}^{{echo}\quad {number}}\frac{a_{n}{\exp \left( {\quad n\quad \theta} \right)}}{2}} + \frac{a_{n}{\exp \left( {{{- }\quad n\quad \theta} - {2\quad \quad \phi}} \right)}}{2}}} & \lbrack 4\rbrack\end{matrix}$

Unless q is substantially larger than f, additional artifact producingsignals may be observed because nq minus if can be close to zero forsome n. If the slice thickness is only two or three times the in planeresolution, as in this application, applying the dephasing gradientalong the slice direction is not specially advantageous and it increasesthe already heavy usage of the slice direction gradient.

Application of the dephasing gradient along the frequency encodedirection makes possible an interpretation of the dephasing as adivision of the signal into two echoes. Either of the two components ofEquation [1] can be rephased. If the dephasing gradient is applied alongthe frequency direction, both components can be observed by leaving thereadout gradient on after acquiring the first component. Separate phaseencoding of the two echoes has been proposed to speed RARE acquisitions.Since a single echo could be acquired with at least twice the bandwidthwithin the same time, there is no intrinsic signal-to-noise ratioimprovement by sampling both echoes. The displaced U-FLARE sequence ofNorris et al. uses a dephasing gradient along the frequency direction.This sequence appears to lack both the initial dephasing gradient andthe rewinding gradient of FIG. 2. The similarity between the twosequences can be seen by recognizing that additional frequency directioncrusher gradients can be applied symmetrically around the refocusingpulses without changing the properties of the sequence. To implement the90° pulse to eliminate the MG component within the displaced U-FLAREsequence would require dephasing the spins, applying the 90° pulse andthen rephasing the spins.

In the current implementation, the dephasing gradient is applied alongthe phase direction. This has the advantage that the prephasing gradientapplied along the readout direction, which centers the echo in thereadout gradients, also can act as a crusher for the sequence. Nocrusher gradients are applied along the phase direction.

Imaging Methods

FIG. 3 illustrates the phase insensitive pulse sequence employed forimaging using the method of the invention. Only the first two echoes areshown; the subsequent echoes are identical except for phase encoding andRF amplitude. Prephasing of the slice gradient is necessary prior to the90° pulse to ensure it properly rotates the non-MG component to thelongitudinal plane. The preparation period must produce transversemagnetization. The pulse sequence of FIG. 3 is identical to the low flipangle RARE sequence previously described except for the presence of thefollowing: the preparation period, the large dephasing gradients in thephase direction applied before the 90 degree pulse and before and aftereach echo, a prephasing pulse in the slice direction designed to cancelthe first half of the slice selection gradient, and a rotation in phaseof the 90 degree pulse by 90 degrees. The functions of these changeswere discussed above.

The phase insensitive RARE sequence of the invention was implemented ona 1.5 T GE SIGNA scanner equipped with a prototype gradient system forfast imaging. The phase encoding and dephasing pulses, which are shownseparately in FIG. 1 for clarity of purpose, were merged in the actualsequence. In all other respects the sequence was identical to the onedescribed in the afore-mentioned Alsop article. An RF train with anasymptotic flip angle of sixty degrees and two echo ramp was employed.The first five refocusing flip angles of the RF pulse train were 142.2°,94.9°, 69.2°, 63.0° and 60.2° with the subsequent flip angles all veryclose to 60°. Though the higher amplitude of the first two echoes couldpotentially be corrected during reconstruction, they were discarded inthis study and centric phase encoding began with the third echo. Thesequence was limited to a phase encode dimension of 64 by an artificialsoftware restriction but the phase direction field of view was reducedto 62.5% of the frequency direction to enhance the phase directionresolution. A frequency direction resolution of 128 and an acquisitionbandwidth of ±32 kHz were chosen. Fields of view between 24 and 28 cmand slice thicknesses between 5 and 8 mm were evaluated. The resultingecho spacings were between 5.1 and 5.3 ms. Though the scanner wascapable of a gradient switching speed of 230 mTm⁻¹ms⁻¹, near theperipheral nerve stimulation threshold, operating at only 77 mTm⁻¹ms⁻¹increased the echo spacing by only 5% and had little impact on imagequality.

Diffusion sensitization was accomplished with a standard Stejskal Tannersequence with a pulse duration, d, of 35 ms, an inter pulse spacing of 6ms and a gradient amplitude of 21 mT/m which corresponds to a b value of1134 s/mm² neglecting imaging gradients and switching time. The timingof the diffusion preparation was selected so the spin echo would occurat the center of the 90 degree pulse of the phase insensitive RAREsequence. Images were acquired with diffusion gradients applied in eachof three directions as well as with very weak diffusion gradients toserve as reference. The effective TE of the zero phase encode was 104ms. Raw echo data were stored and transferred to a workstation forreconstruction and analysis.

Though each excitation produced a single diffusion image, magnitudeaveraging of multiple images was performed to decrease noise and permitmore careful evaluation of image quality. Images were acquired with a TRof 2 seconds and the three diffusion and reference images were acquiredinterleaved in time to minimize any motion that might occur between thedifferent images. A directionally averaged diffusion image was generatedby taking the cube root of the product of the three directional images.This angular averaged image is determined by the trace of the diffusiontensor as can be seen by the following equation. $\begin{matrix}{{\rho \quad {\exp \left( {{- \quad \frac{b}{3}}\left( {D_{xx} + D_{yy} + D_{zz}} \right)} \right)}} = \left( {\left( {\rho \quad {\exp \left( {- {bD}_{xx}} \right)}} \right)\left( {\rho \quad {\exp \left( {{- b}\quad D_{yy}} \right)}} \right)\left( {\rho \quad {\exp \left( {- {bD}_{zz}} \right)}} \right)} \right)^{{- 1}/3}} & \lbrack 5\rbrack\end{matrix}$

where r is the magnetization density and D_(xx), D_(yy) and D_(zz) arethe diagonal components of the diffusion tensor.

The sequence was evaluated in a phantom, two normal volunteers and onepatient. The patient was a 75 year old man with multiple stroke riskfactors who developed right sided visual loss, right hemiparesis, righthemisensory loss and aphasia following a surgical. procedure. Diffusionimaging was performed 48 hours following the onset of symptoms.

Results

The effectiveness of the pulse sequence of the invention has beendemonstrated in a phantom. FIG. 4 illustrates phantom imagesdemonstrating the effect of the 90° pulse at eliminating the non MGcomponent. As shown on the left of FIG. 4, a diffusion weighted imageobtained with the 90° pulse applied at the same phase as the refocusingpulses is free from artifact. Rotation of the 90° pulse phase by 90°produces an image of the non MG component, as shown in the center ofFIG. 4. If the 90° pulse is not employed, the non MG component showsmuch weaker intensity and ghost artifact comparable in magnitude to theimage, as shown on the right of FIG. 4. An image obtained with the 90°pulse turned off demonstrates the artifact introduced by the non-MGcomponent.

FIG. 5 illustrates axial diffusion images of a normal volunteer acquiredwith single-shot RARE. Each image represents the magnitude average of 6single-shot images. Images were acquired with, from left to right, nodiffusion weighting, diffusion gradients applied in the left-rightdirection, anterior-posterior direction and then superior-inferiordirection. The rightmost images are angular average images calculatedfrom the three directional images. All diffusion images employed adiffusion weighting of 1134 s mm⁻².

As shown in FIG. 5, diffusion weighted images in normal subjects showeddiffusion related attenuation but were free from artifact. Anisotropy ofwhite matter was readily apparent in the images acquired with differentdiffusion directions, consistent with previous reports. In the angularaverage images calculated from the three directional images the whitematter was much more uniform in intensity. The angular average imageswere free from artifact associated with image shifts between thedirectional images. Such image shifts frequently appear in echoplanarimages because of the very narrow effective bandwidth of theacquisition.

FIG. 6 illustrates angular average diffusion images from six axialslices in a patient with stroke symptoms, where the upper row wasacquired with zero diffusion weighting and the lower row is an angularaverage of diffusion images acquired in the three directions. Eightaverages were used for each direction prior to calculating the angularaverage image. A primary subcortical lesion within the left occipitaland temporal lobes as well as multiple small foci distributed throughoutthe white matter of the left hemisphere are apparent. Thoughabnormalities are also apparent on the standard clinical T₂ weightedimages, they are much less prominent. The location of the larger lesionis consistent with the clinical symptoms.

Discussion

The phase-insensitive RARE pulse sequence of the invention can produceimages of clinical quality that are highly insensitive to motion. Theuse of tailored RF pulse trains and a 90° pulse to remove the non-MGcomponent were essential to achieving stable echo amplitudes that couldproduce artifact free images. Preparation of the sequence with diffusiongradients produced high quality diffusion images in both normalvolunteers and a patient that were free from the distortion and chemicalshift artifacts that are a frequent problem in echoplanar imaging.Because single-shot MSES are less demanding of hardware than echoplanar,prepared MSES will be more accessible to the clinical community.

The utility of single-shot MSES imaging will depend in part on thesignal-to-noise ratio in comparison to echoplanar or other imagingsequences. In the absence of magnetic field inhomogeneity and chemicalshift differences, an echoplanar acquisition can be as long as a spinecho acquisition with 180° flip angles. Since the presented approach toavoiding phase related artifacts in MSES reduces the signal by a factorof two, the MSES diffusion sequence would clearly be inferior. Inpractice, echoplanar images acquired on the time scale of T₂ areseverely degraded by distortion artifact in many parts of the brain. Ithas been suggested that interleaved echoplanar is necessary to obtainclinical quality diffusion images even with fast gradient systems.Interleaving decreases the effective readout duration and consequentlythe signal-to-noise ratio per unit time and also dramatically increasesthe motion sensitivity. The RARE sequence of the invention employs afrequency direction readout of 2 ms so the sensitivity to chemical shiftand distortion is more than an order of magnitude lower than echoplanar.The excellent image quality obtained without special shimming is clearlyadvantageous. In other parts of the body where the magnetic fieldinhomogeneity can be much worse, MSES diffusion may have a greateradvantage.

Those skilled in the art will appreciate that imaging times almost fourtimes longer than the T₂ of the tissue may be employed using thetechniques of the invention. While T₂ decay during the echo train canlead to blurring of the image, resolution does not appear severelydegraded when the technique of the invention is employed. This canpartially be attributed to the increase in the effective T₂ of thetissue due to stimulated echo components when the refocusing flip angleis low. Simulations indicate that the effective T₂ of tissue isapproximately doubled for a 60° flip angle RF train. A second reason forthe preserved resolution of the images is that the T₂ decay actspartially as a windowing function that reduces ringing artifact nearedges and actually helps to confine the point spread function. T₂ decaymust necessarily cause some loss of resolution and care must be takenwhen choosing long RF trains.

Another issue that arises in comparing MSES with echoplanar, is the timerequired to acquire an image. The image acquisition time for the imagesacquired above was 360 ms, considerably longer than the 64 to 100 msnecessary for echoplanar imaging. The added acquisition time couldreduce the number of slices that can be acquired in a short time. Use offractional k-space acquisition would reduce the RARE acquisition to only150 ms. Since the diffusion preparation requires almost 100 ms, thetotal diffusion imaging time becomes only 250 ms, allowing theacquisition of four slices per second. In practice, many commercialscanner gradient systems would overheat with this many diffusion pulsesper second, so the imaging time is not an excessive burden.

The images in FIGS. 5 and 6 were obtained by magnitude averagingmultiple single-shot images. Though this increases the total imagingtime, the improved signal-to-noise ratio makes it possible to morecarefully assess image quality. In applications like imaging of acutestroke, where the lesion contrast is high and the patients may not becooperative, shorter imaging times may be acceptable, though magnitudeaveraging over two minutes in hyperacute stroke patients has beenreported. In other patients, who can often cooperate through more motionsensitive multi-shot scans that can require over 5 minutes to acquire,averaging may be advantageous. The resolution selected for this studywas selected based on previous echoplanar diffusion studies and the needto achieve a good signal-to-noise ratio. However, thinner slices andhigher resolution are readily achievable with single-shot RARE. Ifdesired, images with resolution comparable to standard clinical T₂ scanscould be obtained but further averaging would be required to increasethe signal-to-noise ratio.

Those skilled in the art will appreciate that numerous othermodifications to the invention are possible within the scope of theinvention. Accordingly, the scope of the invention is not intended to belimited to the preferred embodiments described above, but only by anyappended claims.

I claim:
 1. A phase insensitive method for generating a magnetic resonance image of a sample, the method comprising the steps of: applying a first dephasing magnetic field gradient to the sample to generate a magnetization; applying a first radio frequency pulse to the sample which rotates the magnetization by approximately 90°, the first radio frequency pulse having a phase which is the same as a phase of refocusing pulses of a spin echo sequence to be applied to the sample; applying at least one spin echo sequence whereby a first refocusing pulse of each spin echo sequence occurs at a time after said first radio frequency pulse which is half a time duration between successive refocusing pulses of the spin echo sequence, each spin echo sequence including: a second dephasing magnetic field gradient applied to the sample along the same direction as the first dephasing gradient, a data acquisition period for acquiring data representative of the sample, and a second radio frequency pulse having a sign opposite the first radio frequency pulse; and generating an image of the sample from the data acquired during each data acquisition period.
 2. The method of claim 1, wherein the step of generating the image includes the step of generating the image as a plurality of voxels, and wherein the step of applying the first dephasing magnetic field gradient includes applying the first dephasing magnetic field gradient so that each voxel has equal components of Meiboom-Gill and orthogonal phase.
 3. The method of claim 1, comprising the further step of preparing the sample for diffusion imaging.
 4. The method of claim 1, comprising the further step of preparing the sample for T₂* imaging.
 5. A system for generating a magnetic resonance image of a sample, the system comprising: a magnetic field generator that applies a first dephasing magnetic field gradient to the sample to generate a magnetization; a radio frequency generator that applies a first radio frequency pulse to the sample which rotates the magnetization by approximately 90°, the first radio frequency pulse having a phase which is the same as a phase of refocusing pulses of a spin echo sequence to be applied to the sample; a processor, connected to the magnetic field generator and to the radio frequency generator, that causes at least one spin echo sequence to be generated by said magnetic field generator and radio frequency generator whereby a first refocusing pulse of each spin echo sequence occurs at a time after said first radio frequency pulse which is half a time duration between successive refocusing pulses of the spin echo sequence, each spin echo sequence including: a second dephasing magnetic field gradient applied to the sample along the same direction as said first dephasing gradient, a data acquisition period for acquiring data representative of the sample, and a second radio frequency pulse having a sign opposite the first radio frequency pulse; and a magnetic resonance imaging device that generates an image of the sample from the data acquired during each data acquisition period.
 6. A pulse sequence for application to a magnetic resonance imaging device for imaging a sample, the pulse sequence comprising: a first dephasing magnetic field gradient which is applied to the sample and generates a magnetization; a first radio frequency pulse which is applied to the sample and rotates the magnetization by approximately 90°, the first radio frequency pulse having a phase which is the same as a phase of refocusing pulses of a spin echo sequence to be applied to the sample; and a plurality of spin echo sequences, wherein each said spin echo sequence is applied to the sample whereby a first refocusing pulse of each spin echo sequence occurs at a time after said first radio frequency pulse which is half a time duration between successive refocusing pulses of said spin echo sequence, each said spin echo sequence including: a second dephasing magnetic field gradient which is applied to the sample along the same direction as said first dephasing gradient, and a second radio frequency pulse having a sign opposite the first radio frequency pulse.
 7. The pulse sequence of claim 6, wherein each said spin echo sequence further includes a data acquisition period between said second dephasing magnetic field gradient and said second radio frequency pulse for acquiring data representative of the sample. 